STAT-3 is activated in COPD airway epithelial cells.

Rationale: The airway epithelium (AE) in chronic obstructive pulmonary disease (COPD) displays phenotypic changes including inflammation and epithelial-to-mesenchymal transition (EMT). We addressed whether STAT3, previously linked to both inflammation and EMT, could be activated and mediate EMT in COPD-AE. Methods: AE reconstituted in air-liquid interface (ALI) cultures of human tissue from COPD patients versus (non-)smoker controls, recapitulating the abnormal phenotype observed in situ, were assessed up to 10 weeks for inflammation (IL-8/CXCL-8), EMT (fibronectin, vimentin) and STAT3 activation. Results: We observed increased IL-8/CXCL-8 production (at 1, 2 and 4 weeks) by smoker controls and COPD AE. Similarly, vimentin expression (at 1, 2 and 5 weeks) and fibronectin release (at 1, 2 and 4 weeks) were increased in COPD AEs compared with non-smoker controls. Upregulation of IL-8/CXCL-8, vimentin and fibronectin disappeared at 7 or 8 weeks. STAT3 phosphorylation (Tyr-705) was increased in COPD AEs at 5 weeks (Fig. 1), but no more at 8 weeks. Conclusions: These data show that COPD airway epithelial cells display increased STAT3 activation in vitro, that is concomitant with persistent inflammatory (IL-8/CXCL-8) and EMT features (vimentin, fibronectin) at 5 weeks, and which all regressed at later time-points. Whether STAT3 links inflammation and EMT will be further investigated in this setting.